DNA Fragmentation and Prolonged Expression of c-fos, c-jun, and hsp70 in Kainic Acid-Induced Neuronal Cell Death in Transgenic Mice Overexpressing Human CuZn-Superoxide Dismutase
| Autor: | Charles J. Epstein, Pak H. Chan, Shigeki Mikawa, Jari Honkaniemi, Takeo Kondo, Frank R. Sharp |
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| Rok vydání: | 1997 |
| Předmět: |
0301 basic medicine
Proto-Oncogene Proteins c-jun Apoptosis c-Fos Mice chemistry.chemical_compound 0302 clinical medicine Superoxides Excitatory Amino Acid Agonists In Situ Hybridization Neurons Kainic Acid TUNEL assay biology Superoxide c-jun Brain Genes fos Zinc Neurology Cardiology and Cardiovascular Medicine Proto-Oncogene Proteins c-fos Immediate early gene Kainic acid Free Radicals Recombinant Fusion Proteins Mice Transgenic Nerve Tissue Proteins DNA Fragmentation Immediate-Early Proteins Superoxide dismutase 03 medical and health sciences Genes jun Phagocytosis Seizures Animals Humans HSP70 Heat-Shock Proteins Genes Immediate-Early Superoxide Dismutase Molecular biology Oxidative Stress 030104 developmental biology Gene Expression Regulation nervous system chemistry Terminal deoxynucleotidyl transferase biology.protein Neurology (clinical) Copper 030217 neurology & neurosurgery |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 17:241-256 |
| ISSN: | 1559-7016 0271-678X |
| Popis: | Top of pageAbstract Kainic acid (KA) neurotoxicity was examined in transgenic (Tg) mice overexpressing human CuZn-superoxide dismutase (SOD-1). The doses of KA required to produce seizures, the severity of the seizures, and the regions damaged were similar in SOD-1 Tg and non-transgenic wild-type mice. Intraperitoneal KA injection induced seizure-related neuronal damage in the CA3 and CA1 regions of the hippocampus and in other regions of the brain in both SOD-1 Tg and wild-type mice. These damaged neurons were labeled with the terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL) technique up to 72 h, although no significant difference in the number of TUNEL-positive neurons was observed between SOD-1 Tg and wild-type mice. In situ hybridization showed that c-fos, c-jun, and hsp70 genes were expressed in the hippocampus, cortex, and other regions of the brain after KA treatment. The expression of these genes was maximal 1 to 4 h following KA treatment but persisted longer in the hippocampus and other regions in SOD-1 Tg compared with wild-type mice; however, cell death in the hippocampus, assessed using cresyl violet staining, was similar in SOD-1 Tg and wild-type mice. The data show that superoxide radicals modulate both immediate early gene and heat shock gene expression after KA-induced seizures. The prolonged expression of c-fos, c-jun, and hsp70 in SOD-1 Tg compared with wild-type mice may indicate that hippocampal neurons survive longer in SOD-1 Tg than in wild-type animals: however, cell death as well as the seizure threshold, seizure severity and the pattern of regional vulnerability were not affected substantially by increased levels of SOD in the brain. Keywords: Apoptosis; Heat shock protein; Immediate early gene; Kainic acid; Phagocytosis; Superoxide dismutase; Transgenics Abbreviations: AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; DAB, diaminobenzidine; EAAs, excitatory amino acids; H & E, hematoxylin and eosin; H2O2, hydrogen peroxide; HSP, heat shock protein; IEG, immediate early gene; KA, kainic acid; MCA, middle cerebral artery; NMDA, N-methyl-D-aspartate; O2−, superoxide anion; PBS, phosphate-buffered saline; SSC, standard saline citrate; SOD-1, CuZn-superoxide dismutase; TdT, terminal deoxynucleotidyl transferase; Tg, transgenic |
| Databáze: | OpenAIRE |
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